[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-386459-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-386459-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","antibodydrug-conjugates-adc-in-her2neu-positive-gynecologic-tumors-review","Antibody–Drug Conjugates (ADC) in HER2/neu-Positive Gynecologic Tumors - Review","","Antibody–drug conjugates (ADCs) represent a targeted anti-cancer strategy that links a monoclonal antibody specific for a tumor-surface receptor to a highly cytotoxic payload via engineered cleavable or non-cleavable chemical linkers. HER2 is a key receptor for treating multiple gynecologic tumors. ADCs support selective delivery of cytotoxic agents to tumor cells while reducing exposure of healthy tissues. This review synthesizes approved HER2-targeting ADC literature, relevant preclinical evidence, resistance counter-strategies, and active clinical trials in gynecologic malignancies.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/antibodydrug-conjugates-adc-in-her2neu-positive-gynecologic-tumors-review/386459/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/antibodydrug-conjugates-adc-in-her2neu-positive-gynecologic-tumors-review/386459.png","ImageObject",300,407,{"name":42,"@type":43},"4398046744996","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-29","2026-09-24",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",9,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What are antibody–drug conjugates (ADCs) and how do they work?","Question",{"text":63,"@type":64},"ADCs combine a monoclonal antibody that recognizes a tumor-surface receptor with a cytotoxic payload connected through specific cleavable or non-cleavable linkers. This design aims to deliver the payload preferentially to tumor cells and reduce toxicity in healthy tissues.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"Why is HER2 important for gynecologic tumor treatment?",{"text":68,"@type":64},"HER2 is commonly overexpressed in endometrial and ovarian cancers and is linked to signaling pathways that support malignant cell behaviors. HER2 status is therefore a relevant target for HER2-directed ADC therapies.",{"name":70,"@type":61,"acceptedAnswer":71},"How do cleavable and non-cleavable linkers differ in ADC effects?",{"text":72,"@type":64},"Non-cleavable linkers are described as more stable in serum, while cleavable linkers can show a stronger bystander effect due to greater payload permeability into neighboring cells.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},386459,1790319054,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":11,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":133,"file_id":134,"file_url":135,"file_type":136,"file_size":137,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":138,"language":139,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":12,"update_tm":143,"read_time":144},4398046744996,"molecules   \nReview  \nAntibody–Drug Conjugates (ADC) in HER2/neu-Positive Gynecologic Tumors  \nBlair McNamara , Michelle Greenman , Nicole Pebley , Levent Mutlu  and Alessandro D. Santin *  \nCitation: McNamara, B.; Greenman, M.; Pebley, N.; Mutlu, L.; Santin, A.D. Antibody–Drug Conjugates (ADC) in HER2/neu-Positive Gynecologic Tumors. Molecules 2023, 28, 7389 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)molecules28217389  \nAcademic Editor: Georgia N. Valsami  \nReceived: 13 September 2023  \nRevised: 30 October 2023  \nAccepted: 31 October 2023  \nPublished: 2 November 2023  \nCopyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \nDepartment of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA  \n* Correspondence: [alessandro.santin@yale.edu](alessandro.santin@yale.edu); Tel.: +1-203-737-4450  \nAbstract: Antibody–drug conjugates (ADCs) are a new class of targeted anti-cancer therapies that combine a monoclonal tumor-surface-receptor-targeting antibody with a highly cytotoxic molecule payload bonded through specifically designed cleavable or non-cleavable chemical linkers. One such tumor surface receptor is human epidermal growth factor 2 (HER2), which is of interest for the treatment of many gynecologic tumors. ADCs enable the targeted delivery of a variety of cytotoxic therapies to tumor cells while minimizing delivery to healthy tissues. This review summarizes the existing literature about HER2-targeting ADC therapies approved for use in gynecologic malignancies, relevant preclinical studies, strategies to address ADC resistance, and ongoing clinical trials.  \nKeywords: antibody–drug conjugate; gynecologic malignancy; HER2; ERBB2; chemotherapy; cervical cancer; ovarian cancer; endometrial cancer  \n1. Introduction  \nGynecologic malignancies, a major contributor to worldwide morbidity and mortality, are increasing in incidence and prevalence [1] . Chemotherapy, along with cytoreductive surgery, are fundamental in the treatment of gynecologic malignancies, whether newly diagnosed, recurrent, or metastatic. It is common for patients with recurrence or progression to require several lines and combinations of chemotherapies. Historically, doublet platinum chemotherapy has been widely utilized in these cancers but is associated with significant side effects. The rates of platinum resistance are also high [2] . For these reasons, immunotherapy and targeted drugs are now gaining momentum [3–6] . Given that gynecologic cancers encompass a wide variety of histologic subtypes, each with a host of associated genetic mutations that drive oncogenesis, there is remarkable potential for the use of targeted therapies.  \nState-of-the-art targeted therapies are an exciting new frontier. Antibody drugs are the fastest-growing drug class, with many having been approved for therapeutic use and new antibody drugs in the pipeline [7] . Further antibody–drug conjugates (ADCs) are an opportunity to develop antibodies with novel mechanisms of action that can overcome conventional obstacles, with their efficiency rooted in the selection of the antibody, epitope, payload, linker, and drug-to-antibody ratio (DAR) [7] . ADCs have shown efficacy in other solid malignancies and are now being studied for their use in gynecologic cancers [8] . ADCs are composed of a humanized monoclonal antibody that is complementary to a specific tumor cell surface antigen, a cytotoxic payload, and a linker complex that connects the two (Figure 1) . The payloads are either antimicrotubule compounds or DNA-damaging agents, which have cytotoxicity due to mitotic arrest and cell cycle death (F","cbCaijGHG0Jtb3eB","https://ap.wps.com/l/cbCaijGHG0Jtb3eB","pdf",2217136,14,"English","# Introduction\n## Current treatment background in gynecologic malignancies\n## Role of targeted therapies and ADCs\n## ADC structure and mechanisms\n# HER2 in gynecologic tumors\n## HER2 overexpression across tumor types\n## HER2 signaling and oncogenic effects\n# ADCs in HER2-positive gynecologic cancer\n## Linkers, payloads, and bystander effects\n## Resistance considerations\n# Clinical status and future directions\n## Approved therapies and ongoing trials","[{\"question\":\"What are antibody–drug conjugates (ADCs) and how do they work?\",\"answer\":\"ADCs combine a monoclonal antibody that recognizes a tumor-surface receptor with a cytotoxic payload connected through specific cleavable or non-cleavable linkers. This design aims to deliver the payload preferentially to tumor cells and reduce toxicity in healthy tissues.\"},{\"question\":\"Why is HER2 important for gynecologic tumor treatment?\",\"answer\":\"HER2 is commonly overexpressed in endometrial and ovarian cancers and is linked to signaling pathways that support malignant cell behaviors. HER2 status is therefore a relevant target for HER2-directed ADC therapies.\"},{\"question\":\"How do cleavable and non-cleavable linkers differ in ADC effects?\",\"answer\":\"Non-cleavable linkers are described as more stable in serum, while cleavable linkers can show a stronger bystander effect due to greater payload permeability into neighboring cells.\"}]","Antibody–Drug Conjugates (ADC) in HER2/neu-Positive Gynecologic Tumors - Review | PDF",1790273848,35]